Plasma pharmacokinetics of the mycotoxin deoxynivalenol following oral and intravenous administration to sheep

Abstract

The pharmacokinetics of deoxynivalenol (DON) were studied in sheep after administrating intravenous and oral doses (0.5 and 5.0 mg/kg, respectively). The plasma concentrations were measured using an electron‐capture gas chromatographic method. After iv administration DON plasma levels were found to decrease biexponentially, showing a rapid distribution phase (t_1/2 α=12–23 min), followed by a slower elimination phase (t_1/2 β=57–78 min). Only trace levels of DON could be detected in plasma 7 hr post‐dosing. Further pharmacokinetic data suggest that DON was confined mainly to extracellular fluid, and did not appear to undergo any significant binding or uptake by tissue. After oral dosing, DON was quickly absorbed (t‐max 4.0–5.3 hr), but had a systemic bioavailability of only 7.5%; due in part to its rapid and efficient metabolism by rumen microorganisms. Half‐life of elimination <t_1/2β> was 100–125 min following oral administration, and depending on the animal, required 20–30 hr to be cleared from the system. The metabolic formation of the glucuronide conjugate after iv and oral administration of DON appeared to occur quite efficiently (iv, 21%; oral, 75%), and its elimination half‐lives (iv, 150–200 min; oral 6.1 ‐7.1 hr) were considerably longer than that of the parent toxin. Detection in plasma of the de‐epoxide metabolite, DOM‐1, accounted for only a minor portion of the dose after either dosing regimen (iv, <2.0%; oral, <0.3%), occurring predominantly as the glucuronide conjugate.